7. PROJECT SUMMARY/ABSTRACT Although prostatic adenocarcinoma is the most commonly diagnosed cancer in U.S. males, the death rate from this cancer is lower than would be expected. African Americans (AAs) who have prostate cancer (PCa) typically have more aggressive disease and make up a disproportionate number of the deaths from this disease; however, many patients with PCa will not die of PCa even if untreated (i.e., indolent prostate cancer). We have recently studied the expression of the molecule, Kaiso, in PCa and found that Kaiso is increased in aggressive PCa, especially in PCa in AAs. Also, we have found that Kaiso is involved in facilitating the epigenetic suppression of genes (e.g., E-cadherin), and via this silencing of specific genes, causing epithelial to mesenchymal transition (EMT) and androgen resistance of PCa. The objectives of our proposal are to demonstrate that the nuclear expression of Kaiso is mediated through EGFR signaling and that Kaiso can be targeted therapeutically to reduce EMT and associated metastases of PCa. To accomplish this, we have outlined three specific aims.